Abstract P3-04-25: Role of <i>H19</i>, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells
Bibliographic record
Abstract
Abstract Introduction: Majority of breast cancer tumors are Estrogen receptor positive (ER+) where antiestrogen therapies (endocrine therapies) are the best therapeutic strategy to treat this type of tumors. However, eventually over 30% of patients will develop resistance to endocrine therapies resulting in disease relapse. We recently showed that the long noncoding RNA, H19, is an estrogen target gene that plays a significant role in estrogen-induced proliferation of the normal and malignant ER+ cells. We therefore hypothesize that H19 expression is also important to the proliferation of endocrine therapy resistant cells. In this study, we examined if estrogen-independent H19 expression is important to the development of endocrine therapy resistance. Objective: The overall objective of this project is to use therapy sensitive (MCF-7) and therapy-resistant (LCC9) breast cancer cells as model systems to examine the role of long non-coding RNA H19 in development and maintenance of resistance to endocrine therapy. Methodology and Results: We examined the expression of H19 in ER+ breast cancer cells (MCF7) that under the selective pressure of fulvesterant (ICI, ER down regulator) acquire resistance to ICI. We observed that while H19 expression was initially decreased as expected, its expression subsequently increased in the ICI-resistant MCF7 cells. Interestingly, H19 knockdown in MCF7 cells significantly decrease their proliferation as determined by Flowcytometry and made them more sensitive to ICI. We also examined H19 expression in the ICI-resistant LCC9 cells and found that ICI treatment increased H19 expression. Interestingly, H19 knockdown in the LCC9 cells decreased their proliferation and surprisingly made them sensitive to ICI treatment. Previous observations indicate that NOTCH4 receptor (NR4) may be involved in endocrine therapy resistance. Interestingly we found that in presence of ICI, NR4 expression is increased and that forced activation of NR4 markedly increases H19 expression in LCC9 cells. Conclusion: Altogether these observations suggest that H19 plays an important role in the development of endocrine therapy resistance and further our understanding of the cellular and molecular mechanisms involved in endocrine therapy resistance. These and similar studies could potentially lead to the development of new therapies to treat therapy resistant tumor cells. Further experiments would reveal if signalling pathways that regulate H19 expression independent of estrogen are useful therapies against endocrine therapy resistant tumors. Citation Format: Basak P, Chatterjee S, Bhat V, Jin H, Su A, Murphy LC, Raouf A. Role of H19, a long non-coding RNA, in development of resistance to endocrine therapy in breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-25.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".